ArticleCancer science2023
Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation.
Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets.Biomarker research · 2026Review
- Prognostic significance of co-expression of c-MET and EGFR in locally advanced and metastatic gastric cancer: a retrospective cohort study.Frontiers in oncology · 2026Article
- FDA-approved kinase inhibitors in PROTAC design, development and synthesis.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- An overview of hepatitis B virus in gastric carcinogenesis: from clinical association to molecular mechanisms.Infectious agents and cancer · 2025Review
- Development of dual aptamers-functionalized c-MET PROTAC degraders for targeted therapy of osteosarcoma.Theranostics · 2025Article
- Targeting the Wnt/β-catenin pathway and epithelial-mesenchymal transition in gastric cancer: mechanisms, therapeutic strategies, and clinical challenges.Frontiers in oncology · 2025Review
- The MET Oncogene: An Update on Targeting Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- AberrantCells · 2024Review
- Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation.Cancer science · 2023Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the "occupancy-driven" model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.